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Vol. 12, Issue 10, 2987-3003, October 2001
*Departments of Biochemistry and ¶Genetics, and
#Howard Hughes Medical Institute, Stanford University
School of Medicine, Stanford, California 94305; and
§Department of Biochemistry and ##Howard Hughes
Medical Institute, Baylor College of Medicine, Houston, Texas 77030
Eukaryotic cells respond to DNA damage by arresting the cell
cycle and modulating gene expression to ensure efficient DNA repair.
The human ATR kinase and its homolog in yeast, MEC1, play central roles in transducing the damage signal. To characterize the
role of the Mec1 pathway in modulating the cellular response to DNA
damage, we used DNA microarrays to observe genomic expression in
Saccharomyces cerevisiae responding to two different
DNA-damaging agents. We compared the genome-wide expression patterns of
wild-type cells and mutants defective in Mec1 signaling, including
mec1, dun1, and crt1 mutants, under
normal growth conditions and in response to the methylating-agent
methylmethane sulfonate (MMS) and ionizing radiation. Here, we present
a comparative analysis of wild-type and mutant cells responding to
these DNA-damaging agents, and identify specific features of the gene
expression responses that are dependent on the Mec1 pathway. Among the
hundreds of genes whose expression was affected by Mec1p, one set of
genes appears to represent an MEC1-dependent expression signature of DNA damage. Other aspects of the genomic responses were independent of
Mec1p, and likely independent of DNA damage, suggesting the pleiotropic
effects of MMS and ionizing radiation. The complete data set as well as
supplemental materials is available at
http://www-genome.stanford.edu/mec1.
These authors contributed equally to this work.
Present addresses:
Lawrence Berkeley National Lab,
Berkeley, CA 94720;
Department of Biochemistry and
Molecular Genetics, University of Colorado Health Science Center,
Denver, CO 80262.
@
Corresponding author. E-mail address:
pbrown{at}cmgm.stanford.edu.
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